Linking microRNA dysfunction and neurological diseases.

Although progress in our understanding of the genetic basis of Spinal Muscular Atrophy, molecular functions of SMN and development of animal models of the disease are paving the way to the identification of the molecular mechanisms of Spinal Muscular Atrophy pathogenesis, the defect responsible for the specific degeneration of motor neurons in the spinal cord of Spinal Muscular Atrophy patients remains elusive. To understand Spinal Muscular Atrophy pathophysiology, recent efforts have been focusing on the characterization of SMN activity and the consequence of its deficiency in both cellular and animal model systems.

The fact that most of the Gemin3 and Gemin4 proteins are found in the SMN complex (Charroux et al. 1999, 2000), but are also found in microRNPs, raises the intriguing possibility that the SMN complex, a key factor in the biogenesis and function of diverse RNPs, may intersect with the pathways in which miRNPs function or that deletion or loss-of-function mutations of SMN in Spinal Muscular Atrophy patients may also affect the activity of miRNPs due to possible redistribution or changes in the levels of Gemin3 and Gemin4. Gemin3 and Gemin4 may be common components of all miRNPs or may be associated with a subset of the Argonaute proteins resulting in miRNPs with specific properties. Thus, specific or general changes in the activity of the miRNPs may play a role in the development of Spinal Muscular Atrophy and it will be of great interest to analyze the role of miRNA in this devastating neurodegenerative disease.